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Are Structural Changes Induced by Lithium in the HIV Brain Accompanied by Changes in Functional Connectivity?

Tivarus ME, Pester B, Schmidt C, Lehmann T, Zhu T, Zhong J, Leistritz L, Schifitto G - PLoS ONE (2015)

Bottom Line: Specifically, we found that lithium treatment in this population induced changes suggestive of increased strength in functional connectivity.Therefore, by exploiting the information about the strength of functional interactions provided by gPDC we can quantify the connectivity changes observed in relation to a given intervention.Furthermore, in conditions where the intervention is associated with clinical changes, we suggest that this methodology could enable an interpretation of such changes in the context of disease or treatment induced modulations in functional networks.

View Article: PubMed Central - PubMed

Affiliation: Department of Imaging Sciences, University of Rochester Medical Center, Rochester, New York, United States of America.

ABSTRACT
Lithium therapy has been shown to affect imaging measures of brain function and microstructure in human immunodeficiency virus (HIV)-infected subjects with cognitive impairment. The aim of this proof-of-concept study was to explore whether changes in brain microstructure also entail changes in functional connectivity. Functional MRI data of seven cognitively impaired HIV infected individuals enrolled in an open-label lithium study were included in the connectivity analysis. Seven regions of interest (ROI) were defined based on previously observed lithium induced microstructural changes measured by Diffusion Tensor Imaging. Generalized partial directed coherence (gPDC), based on time-variant multivariate autoregressive models, was used to quantify the degree of connectivity between the selected ROIs. Statistical analyses using a linear mixed model showed significant differences in the average node strength between pre and post lithium therapy conditions. Specifically, we found that lithium treatment in this population induced changes suggestive of increased strength in functional connectivity. Therefore, by exploiting the information about the strength of functional interactions provided by gPDC we can quantify the connectivity changes observed in relation to a given intervention. Furthermore, in conditions where the intervention is associated with clinical changes, we suggest that this methodology could enable an interpretation of such changes in the context of disease or treatment induced modulations in functional networks.

No MeSH data available.


Related in: MedlinePlus

Post lithium treatment time-variant and frequency-selective functional connectivity maps obtained by gPDC (median over all subjects, for a representative run); ROI1: Right cerebellum, ROI2: Right putamen, ROI3: Right medial frontal gyrus, ROI4: Left orbital gyrus, ROI5: Right orbital gyrus, ROI6: Right lateral occipital cortex, ROI7: Right subcallosal gyrus.
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pone.0139118.g003: Post lithium treatment time-variant and frequency-selective functional connectivity maps obtained by gPDC (median over all subjects, for a representative run); ROI1: Right cerebellum, ROI2: Right putamen, ROI3: Right medial frontal gyrus, ROI4: Left orbital gyrus, ROI5: Right orbital gyrus, ROI6: Right lateral occipital cortex, ROI7: Right subcallosal gyrus.

Mentions: To provide an overall impression of the resulting networks, median gPDC values of all subjects for pre and post lithium treatment for one representative run are presented in Figs 2 and 3. In this illustration, a time-frequency map in the i-th row and j-th column represents the time-variant, frequency-selective degree of effective connectivity from ROI j to ROI i. A qualitative comparison between Figs 2 and 3 suggests that in general gPDC values slightly increase from pre to post treatment status. However, this is merely descriptive and specific connectivity patterns are hardly identifiable due to the high amount of output data [29]. Therefore, an exhaustive evaluation of these raw results required further processing steps. This was accomplished by the already described combination of gPDC-based network measures and the subsequent statistical analysis. This detailed analysis confirmed the aforementioned descriptive assumption, namely a global lithium treatment effect on functional connectivity characteristics.


Are Structural Changes Induced by Lithium in the HIV Brain Accompanied by Changes in Functional Connectivity?

Tivarus ME, Pester B, Schmidt C, Lehmann T, Zhu T, Zhong J, Leistritz L, Schifitto G - PLoS ONE (2015)

Post lithium treatment time-variant and frequency-selective functional connectivity maps obtained by gPDC (median over all subjects, for a representative run); ROI1: Right cerebellum, ROI2: Right putamen, ROI3: Right medial frontal gyrus, ROI4: Left orbital gyrus, ROI5: Right orbital gyrus, ROI6: Right lateral occipital cortex, ROI7: Right subcallosal gyrus.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4593570&req=5

pone.0139118.g003: Post lithium treatment time-variant and frequency-selective functional connectivity maps obtained by gPDC (median over all subjects, for a representative run); ROI1: Right cerebellum, ROI2: Right putamen, ROI3: Right medial frontal gyrus, ROI4: Left orbital gyrus, ROI5: Right orbital gyrus, ROI6: Right lateral occipital cortex, ROI7: Right subcallosal gyrus.
Mentions: To provide an overall impression of the resulting networks, median gPDC values of all subjects for pre and post lithium treatment for one representative run are presented in Figs 2 and 3. In this illustration, a time-frequency map in the i-th row and j-th column represents the time-variant, frequency-selective degree of effective connectivity from ROI j to ROI i. A qualitative comparison between Figs 2 and 3 suggests that in general gPDC values slightly increase from pre to post treatment status. However, this is merely descriptive and specific connectivity patterns are hardly identifiable due to the high amount of output data [29]. Therefore, an exhaustive evaluation of these raw results required further processing steps. This was accomplished by the already described combination of gPDC-based network measures and the subsequent statistical analysis. This detailed analysis confirmed the aforementioned descriptive assumption, namely a global lithium treatment effect on functional connectivity characteristics.

Bottom Line: Specifically, we found that lithium treatment in this population induced changes suggestive of increased strength in functional connectivity.Therefore, by exploiting the information about the strength of functional interactions provided by gPDC we can quantify the connectivity changes observed in relation to a given intervention.Furthermore, in conditions where the intervention is associated with clinical changes, we suggest that this methodology could enable an interpretation of such changes in the context of disease or treatment induced modulations in functional networks.

View Article: PubMed Central - PubMed

Affiliation: Department of Imaging Sciences, University of Rochester Medical Center, Rochester, New York, United States of America.

ABSTRACT
Lithium therapy has been shown to affect imaging measures of brain function and microstructure in human immunodeficiency virus (HIV)-infected subjects with cognitive impairment. The aim of this proof-of-concept study was to explore whether changes in brain microstructure also entail changes in functional connectivity. Functional MRI data of seven cognitively impaired HIV infected individuals enrolled in an open-label lithium study were included in the connectivity analysis. Seven regions of interest (ROI) were defined based on previously observed lithium induced microstructural changes measured by Diffusion Tensor Imaging. Generalized partial directed coherence (gPDC), based on time-variant multivariate autoregressive models, was used to quantify the degree of connectivity between the selected ROIs. Statistical analyses using a linear mixed model showed significant differences in the average node strength between pre and post lithium therapy conditions. Specifically, we found that lithium treatment in this population induced changes suggestive of increased strength in functional connectivity. Therefore, by exploiting the information about the strength of functional interactions provided by gPDC we can quantify the connectivity changes observed in relation to a given intervention. Furthermore, in conditions where the intervention is associated with clinical changes, we suggest that this methodology could enable an interpretation of such changes in the context of disease or treatment induced modulations in functional networks.

No MeSH data available.


Related in: MedlinePlus